Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study

Abstract

Background: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). Objectives: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. Method: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell’s C statistics, and Royston’s explained variation in univariable and multivariable analyses. Results: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. Conclusions: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms

“…The sub classification into NET G3 and NEC has recently been validated for its prognostic relevance, and survival of patients with NET G3 is significantly better compared to patients with NEC [4,9,10]. However, assessing the degree of differentiation by histopathological criteria may be challenging and consensus is difficult to obtain even among expert pathologists [11,12].…”

High-Grade Progression Confers Poor Survival in Pancreatic Neuroendocrine Tumors

“…Indeed, this disease shows an extraordinary spectrum of cell proliferation ranging from a Ki-67 index of ∼0 to ∼100%. Tumor morphology and Ki-67 index provide prognostic and predictive information and defines the World Health Organization (WHO) grading system: Grade 1, Ki-67 index < 3%; grade 2, Ki-67 index 3-20%; grade 3 neuroendocrine tumor, welldifferentiated morphology and Ki-67 index > 20%; and grade 3 neuroendocrine carcinoma (NEC), poorly differentiated morphology and Ki-67 index > 20% [7,8].…”

Classification of neuroendocrine neoplasms: lights and shadows

“…Pancreatic NENs (PanNENs) are the tumors where the prognostic role of Ki67 proliferative index has been most investigated during the last years [72][73][74][75] and it represents an important prognostic marker together with stage [75]. The current WHO classification is very useful to stratify patients with PanNENs in different prognostic categories and its use is strongly recommended.…”